The ferritin-heavy chain (FTH1) is the catalytic subunit of the ferroxidase ferritin, which prevents oxidative DNA damage via intracellular iron storage. FTH1 was shown to be a prognostic marker for triple-negative breast cancer (BC) patients and associated with an enrichment of CD8+ effector T cells. However, whether the expression and localization of FTH1 are also associated with clinical outcome in other BC subtypes is unknown. Here, we investigated the association of FTH1 with time to survival in BCs from 222BRCA1/2mutation carriers by immunohistochemistry on tissue microarrays. In addition, for 51 of these patients, the association between FTH1 and specific subsets of T cells was evaluated on whole slides using automatic scoring algorithms. We revealed that nuclear FTH1 (nFTH1) expression, in multivariable analyses, was associated with a shorter disease-free (HR = 2.71, 95% CI = 1.49–4.92,p= 0.001) and metastasis-free survival (HR = 3.54, 95% CI = 1.45–8.66,p= 0.006) in patients carrying aBRCA1/2mutation. However, we found no relation between cytoplasmic FTH1 expression and survival ofBRCA1/2mutation carriers. Moreover, we did not detect an association between FTH1 expression and the amount of CD45+ (p= 0.13), CD8+ (p= 0.18), CD4+ (p= 0.20) or FOXP3+ cells (p= 0.17). Consequently, the mechanism underlying the worse recurrence-free survival of nFTH1 expression inBRCA1/2mutation carriers needs further investigation.
铁蛋白重链（FTH1）是铁氧化酶铁蛋白的催化亚基，通过细胞内铁储存防止氧化性DNA损伤。研究表明，FTH1是三阴性乳腺癌患者的预后标志物，并与CD8+效应T细胞的富集相关。然而，FTH1的表达和定位是否与其他乳腺癌亚型的临床结局相关尚不清楚。本研究通过组织芯片免疫组化技术，对222例BRCA1/2突变携带者的乳腺癌样本进行FTH1与生存时间的关联性分析。此外，针对其中51例患者，采用自动评分算法在全切片上评估了FTH1与特定T细胞亚群的关系。多变量分析显示，在BRCA1/2突变携带者中，细胞核FTH1（nFTH1）表达与较短的无病生存期（HR = 2.71，95% CI = 1.49–4.92，p = 0.001）和无转移生存期（HR = 3.54，95% CI = 1.45–8.66，p = 0.006）显著相关。然而，细胞质FTH1表达与BRCA1/2突变携带者的生存期无显著关联。此外，未发现FTH1表达与CD45+（p = 0.13）、CD8+（p = 0.18）、CD4+（p = 0.20）或FOXP3+细胞数量（p = 0.17）存在相关性。因此，BRCA1/2突变携带者中nFTH1表达导致无复发生存期缩短的机制仍需进一步研究。
肿瘤(癌症)患者之家